HIV-1 infection of CD34+ progenitor cells may explain, in part, the defective lymphopoiesis in HIV-1 infected individuals, even those undergoing highly active anti-retroviral therapy (HAART). It is currently not known if peripheral T cell re-expansion alone can restore immunocompetence following severe T cell depletion in certain HIV-1 infected individuals. T cell regeneration by thymic and extrathymic pathways may be delayed or defective due to HIV damage or may be suppressed by HAART. Previous work by others has demonstrated T cell lymphopoiesis in peripheral lymphoid tissue in athymic nu/nu mice in the absence of the thymus. Utilizing an in vitro organotypic model of human immunopoiesis, preliminary evidence suggests an extrathymic route of T cell lymphpoiesis can be induced in vitro in peripheral lymphoid tissue from both HIV-1+ long term non- progressor (LTNP) and patients with advanced HIV-1 disease. Currently, the quality and character of de novo T cell lymphopoiesis from secondary lymphoid tissue obtained from patients with advanced HIV disease with degenerative changes in lymph node architecture is being evaluated following cytokine conditioning and reconstitution with autologous CD34+ progenitor cells.